Oxime carbamate phosphate, phosphonate, phosphinate and phosphoroamidates

ABSTRACT

Oxime carbamate phosphates, phosphonates, phosphinates and phosphoroamidates having the general formula: IN WHICH X and Y are independently selected from the group consisting of oxygen and sulfur; R is selected from the group lower alkyl or lower alkoxy, having from one to six carbon atoms inclusive; R1 is selected from the group consisting of lower alkyl or lower alkoxy having from one to six carbon atoms, inclusive, amino, lower alkyl-substituted amino and phenyl; Q is selected from the group consisting of divalent tetramethylenediene-1, 3, lower alkoxy or lower alkyl having from one to four carbon atoms inclusive, each, nitro, halogen and combinations thereof, and lower dialkyl-substituted thionophosphoryloxy; R2 is selected from the group consisting of hydrogen, lower alkyl having from one to four carbon atoms, and phenyl; and R3 is selected from the group consisting of hydrogen; substituted carbonate and thiocarbonates of the type IN WHICH Z is oxygen or sulfur, R4 is lower alkyl having from one to four carbon atoms, inclusive, and Beta -chloro-loweralkyl having from two to four carbon atoms; carbamates of the type IN WHICH R5 and R6 are independently selected from the group consisting of hydrogen, alkyl having from one to 10 carbons, inclusive, substituted alkyl having one to six carbon atoms inclusive, said substituents selected from the group consisting of hydroxy, halogen, amino, di-lower-alkyl amino, lower alkoxy, and tetrahydrofuryl; lower alkenyl having from two to four carbons, inclusive, carboalkoxy alkyl having a total of from three to eight carbon atoms, inclusive, cycloalkyl having from three to six carbon atoms, inclusive, piperazino, 2-thiazolyl, phenyl, naphthyl, substituted phenyl wherein said substituents are selected from the group consisting of halogen, lower alkyl, lower alkoxy, lower thioalkyl, lower dialkylamino in which said lower alkyl and lower alkoxy moieties have from one to four carbon atoms, inclusive, nitro, cyano, trifluoromethyl, and combinations thereof; and in which IS AN N-containing heterocyclic member selected from the group consisting of morpholino, piperazino, pyrrolidino, piperidino, hexamethyleneimino, pyrryl, indolyl, imidazolyl, benzimidazolyl, pyrazolyl, 1,3-oxazolidino, and 1,3-thiazolidino, esters of the type WHEREIN R7 is selected from the group consisting of alkyl having from one to eight carbons inclusive, trichloromethyl, and lower alkenyl having from two to four carbon atoms, inclusive, and the radical -(CH2)m-SR in which m is 1 or 2, R is alkyl having one to six carbon atoms, alkenyl having two to four carbon atoms, phenyl, substituted phenyl in which said substituents are selected from the group halogen, lower alkyl having one to four carbon atoms, inclusive, and lower alkoxy having one to four carbon atoms, inclusive; lower alkyl sulfonato having from one to six carbon atoms, inclusive; lower alkyl substituted thiophosphoryl wherein the lower alkyl groups independently contain from one To four carbon atoms, inclusive, and 2,2,2trichloro-1-hydroxyethyl, 4-cyanophenyl, 2,4,5-trichlorophenyl and 4-methylthiophenyl. The compounds are useful as insecticides, animal contact and systemic parasiticides, herbicides and foliar fungi protectants. Representative compounds are: 3-(O,O-diethylphosphorothioyl) benzaldoxime; 3-(O-(0,0-diethylphosphorothioyl))-benzaldoximinoN&#39;&#39;-methyl carbamate, 4(O-O,O-diethylphosphorothioyl))acetophenone oxime; 4-(O,O-diethylphosphorothioyl))acetophenoneoximino-N&#39;&#39;-methyl carbamate; and 4-(O,Odiethylphosphorothioyl)-acetophenoneoximino acetate; 4-(O-(O,ODiethylphosphorothioyl))-benzaldoximino-N&#39;&#39;-morpholinyl carbamate; 4-(O-(O,O-Diethylphosphorothioyl))-benzaldoximino-N&#39;&#39;-piperidyl carbamate; 4-(O,O-Diethylphosphorothioyl))-benzaldoximino-N&#39;&#39;azepinocarbamate; 0-Ethyl-0-(4-(N&#39;&#39;-methylcarbamyloximino)phenyl)-N-methylamido phosphorothioate; 4-(O,ODiethylphosphorothioyl))-benzaldoximino-N&#39;&#39;-( Beta -N&#39;&#39;&#39;&#39;, N&#39;&#39;&#39;&#39;diethylaminoethyl)-carbamate.

EJIBNQ Gutman tates atettt OXIME CARBAMATE PHOSPTE,

PHOSPHONATE, PHOSPNATE AND PHGSPHGROADATES [7 2] Inventor: Arnold D. Gutman, Berkeley, Calif.

Stauffer Chemical Company, New York, NY.

[22] Filed: June 25, 1970 211 App]. No.: 49,937

Related us. Application Data [60] Division of Ser. No. 730,588, May 20, 1968, abandoned, which is a continuation-in-part of Ser. No. 646,467, June 16, 1967, abandoned.

[73] Assignee:

Primary ExaminerJoseph Rebold Assistant ExaminerAnton H. Sutto Att0rneyDaniel C. Block, Edwin H. Baker, Albert J. Adamcik and Harry A. Pacini [57] ABSTRACT Oxime carbamate phosphates, phosphonates, phosphinates and phosphoroamidates having the general formula:

in which X and Y are independently selected from the group consisting of oxygen and sulfur; R is selected from the group lower alkyl or lower alkoxy, having from one to six carbon atoms inclusive; R is selected from the group consisting of lower alkyl or lower alkoxy having from one to six carbon atoms, inclusive, amino, lower alkyl-substituted amino and phenyl; Q is selected from the group consisting of divalent tetramethylenediene-l, 3, lower alkoxy or lower alkyl having from one to four carbon atoms inclusive, each, nitro, halogen and combinations thereof, and lower dialkyl-substituted thionophosphoryloxy; R is selected from the group consisting of hydrogen, lower alkyl having from one to four carbon atoms, and phenyl; and R is selected from the group consisting of hydrogen; substituted carbonate and thiocarbonates of the type in which Z is oxygen or sulfur, R is lower alkyl having from one to four carbon atoms, inclusive, and ,8- chloro-loweralky1 having from two to four carbon atoms; carbamates of the type [451 Aug.1,1972

in which R and R are independently selected from the group consisting of hydrogen, alkyl having from one to 10 carbons, inclusive, substituted alkyl having one to six carbon atoms inclusive, said substituents selected from the group consisting of hydroxy, halogen, amino, di-lower-alkyl amino, lower alkoxy, and tetrahydrofuryl; lower alkenyl having from two to four carbons, inclusive, carboalkoxy alkyl having a is an N-containing heterocyclic member selected from the group consisting of morpholino, piperazino, pyrrolidino, piperidino, hexamethyleneimino, pyrryl, indolyl, imidazolyl, benzimidazolyl, pyrazolyl, 1,3-0xazolidino, and 1,3-thiazolidino, esters of the type wherein R is selected from the group consisting of alkyl having from one to eight carbons inclusive,

trichloromethyl, and lower alkenyl having from two to four carbon atoms, inclusive, and the radical (CH ,,,--SR in which m is 1 or 2, R is alkyl having one to six carbon atoms, alkenyl having two to four carbon atoms, phenyl, substituted phenyl in which said substituents are selected from the group halogen, lower alkyl having one to four carbon atoms, inclusive, and lower alkoxy having one to four carbon atoms, inclusive; lower alkyl sulfonato havingfrom one to six carbon atoms, inclusive; lower alkyl substituted thiophosphoryl wherein the lower alkyl groups independently contain from one to four carbon atoms, in-

clusive, and 2,2,2-trichlorol-hydroxyethyl, 4- cyanophenyl, 2,4,5-trichlorophenyl and 4- methylthiophenyl.

The compounds are useful as insecticides, animal contact and systemic parasiticides, herbicides and foliar fungi protectants. Representative compounds are: 3- [0,0-diethylphosphorothioyl] benzaldoxime; 3-[0- (0,0-diethylphosphorothioyl)]-benzaldoximino-N'- methyl carbamate, 4[O-0,0- diethylphosphorothioyl)]acetophenone oxime; 4- [0,0-diethylphosphorothioyl)]-acetophenoneoximino-N-methyl carbamate; and 4-(0,0- diethylphosphorothioyl)-acetophenoneoximino acetate; 4-[O-(0,0-Diethylphosphorothioyl)]-benzaldoximino-N-morpholinyl carbamate; 4-[O-(0,0- Diethylphosphorothioyl) ]-benzaldoximino-N- United States Patent Gutman piperidyl carbamate; 4-[0,0- Diethylphosphorothioyl)]-benzaldoximino-N'- azepinocarbamate; O-Ethyl-O-[4-(N'-methylcarbamyl- [451 Aug. 1, 1972 [0,0-Diethylphosphoroxhioyl)]-benz.ldoximino-N'- (,B-N' N '-diethylaminoethyl)-carbamate.

4 Claims, No Drawings OXDVIE CARBAMATE PHOSPHATE, PHOSPHONATE, PHOSPIHNATE AND PHOSPHOROAMIDATES This application is a division of copending application, Ser. No. 730,588, filed May 20, 1968, now abandoned which application is a continuation-in-part of then copending application, Ser. No. 646,467, filed June 16, 1967, now abandoned.

This invention relates to certain novel phosphorus containing compounds which can be used as insecticides, animal parasiticides, both contact and systemic, herbicides and foliage fungi protectants. More specifically, this invention relates to certain substituted organo-oxime phosphates, phosphonates, phosphinates and phosphoroamidates and to the preparation and utility of the compounds as insecticides, animal systemic parasiticides, herbicides and foliage fungicides.

The compound comprising the instant class of compounds correspond to the general formula:

in which X AND Y are independently selected from the group consisting of oxygen and sulfur; R is selected from the group lower alkyl or lower alkoxy, having from one to six carbon atoms, inclusive; R is selected from the group consisting of lower alkyl or lower alkoxy having from one to six carbon atoms, inclusive, amino, lower alkyl-substituted amino, and phenyl; Q is selected from the group consisting of divalent tetramethylenediene-l,3, lower alkoxy or lower alkyl having from one to four carbon atoms inclusive, each, nitro, halogen and combinations thereof, and lower dialkyl substituted thionophosphoryloxy; R is selected from the group consisting of hydrogen, lower alkyl having from one to four carbon atoms and phenyl; and R is selected from the group consisting of hydrogen substituted carbonate and thiocarbonates of the type in which Z is oxygen or sulfur, R is lower alkyl having from one to four carbon atoms, inclusive, and B chloroloweralkyl having from two to four carbon atoms; carbamates of the type in which R, and R are independently selected from the group consisting of hydrogen, alkyl having from one to 10 carbons, inclusive, substituted alkyl having one to six carbon atoms inclusive, said substituent is selected from the group consisting of hydroxy, halogen, amino, di-lower alkyl amino, lower alkoxy and tetrahydrofuryl; lower alkenyl having from two to four carbons, inclusive, carboalkoxy alkyl having a total of from three to eight carbon atoms, inclusive, cycloalkyl having from three to six carbon atoms, inclusive, piperazino, 2- thiazolyl, phenyl, naphthyl, substituted phenyl wherein said substitutents are selected from the group consisting of halogen, lower alkyl, lower alkoxy, lower thioalkyl, lower dialkylamino in which said lower alkyl and lower alkoxy moieties have from one to four carbon atoms, inclusive, nitro, cyano, trifluoromethyl and combinations thereof; and in which is an N-containing heterocyclic member selected from the group consisting of morpholino, piperazino, pyrrolidino, piperidino, hexamethyleneimino, pyrryl, indolyl, imidazoyl, benzimidazolyl, pyrazolyl, 1,3-oxazolidino, and 1,3-thiazolidino; esters of the types wherein R is selected from the group consisting of alkyl having from one to eight carbons, inclusive, trichloromethyl, and lower alkenyl having from two to four carbon atoms, inclusive, and the radical (CH -SR in which m is l or 2, R is alkyl having one to six carbon atoms, alkenyl having two to four carbon atoms, phenyl, substituted phenyl in which said substituents are selected from the group halogen, lower alkyl having one to four carbon atoms, inclusive and lower alkoxy having one to four carbon atoms, inclusive; lower alkyl sulfonato having from one to six carbon atoms, inclusive; loweralkyl substituted thiophosphoryl wherein the lower alkyl groups independently contain from one to four carbon atoms, inclusive; and 2,2,2-trichloro-l-hydroxyethyl, 4- cyanophenyl, 2,4,5-trichlorophenyl and 4- methylthiophenyl. Lower alkyl and lower alkoxy includes those members of the groups which contain the indicated number of carbon atoms in both straight chain and branched chain configurations; Lower alkenyl includes those members of the group containing a double bond and containing from two to four carbon atoms, inclusive. When Q is divalent tetramethylenel,3' it is bonded to the 2,3 or 3,4 carbon atoms of the phenyl ring, thereby becoming eithera or ,8 naphthyl, respectively. Also included herein is a method of preparing, using, and applying the compositions.

The compounds herein described can be prepared by several methods. One such general method applicable in preparing the compounds is the condensation between the appropriate substituted phosphorus-containing oxy or thio benzaldehyde, e.g. phosphoro, phosphono, and phosphino, and hydroxylamine hydrochloride in order to prepare the corresponding benzaldoxime. The benzaldoxime can be further reacted with appropriate substituted isocyanate, substituted acid chlorides, substituted chloroformate, substituted chlorothiolformate, substituted sulfonyl chloride, monosubstituted carbamyl chloride, N,Ndisubstituted carbamyl chloride, substituted phosphoryl chloride, substituted thionophosphoryl chloride, or anhydrous trichloro-acetaldehyde. When R is to be lower alkyl, an appropriate substituted-phosphoryl or substituted-thiophosphoryl lower alkyl phenylketone is condensed with hydroxylarnine hydrochloride to prepare the corresponding ketoxime. Another method useful for the preparation of carbamyl derivatives is first the condensation of phosgene with the aldoxime followed by the condensation with a primary or secondary amine. The reactions proceed readily in the liquid phase. The employment of a solvent is also useful, facilitating processing, as well as agitation of the reactants. Solvents such as water, benzene, toluene, chloroform, aqueous ethanol and the like, can be employed. When using derivatives containing the aldoxime, it is preferred to carry out the reaction in the presence of a hydrogen halide acceptor such as sodium carbonate, triethylarnine, pyridine, picoline and the like, which are used as catalysts. Similarly, in the condensation reaction to prepare secondary carbamyl derivatives, the reaction is preferably conducted in the presence of a hydrogen halide acceptor.

The reactions are carried out at temperatures that permit operation in the liquid phase. These temperatures are between about room temperature and reflux temperature of the solvent, if one is employed. Preferably, the reaction mixture is refluxed, usually at an elevated temperature. The ketoxirne can be reacted with functional moieties as described supra for the benzaldoxime.

It now has been discovered that the new compositions disclosed herein are distinguished as useful as insecticides, herbicides, foliar fungi protectants and are particularly effective as systemic parasiticidal agents for animals.

The compounds of the present invention are prepared in accordance with the following illustrative examples.

EXAMPLE 1 Preparation of the Intermediate diethylphosphorothioyl)] Benzaldehyde In 200 ml. of methyl ethyl ketone in a 500 ml. threeneck flask are combined 24.4 g. (0.2 moles) 3-hydroxybenzaldehyde, 37.8 g. (0.2 moles) 0,0- diethylthiophosphorylchloride, and 16.4 g. (0.12 moles) potassium carbonate. The mixture is stirred and heated under reflux for 4 hours, cooled, and poured into 300 ml. of water. The mixture is filtered free of solid and is extracted with two 1.50 ml. portions of chloroform. The chloroform phases are combined, dried with anhydrous MgSO. and the solvent evaporated. There is obtained 54.7 g. (99.5 percent of theory) of the title intermediate, n 1.5239.

Preparation of 3-[0,0-diethylphosphorothioyl] benzaldoxirne.

' in 300 ml. of water are combined 27.4 g. (0.1 moles) 3-[O-(0,0-diethylphosphorothioyl)]-benzaldehyde and 7.6 g. (0.1 moles) hydroxylamine hydrochloride. The mixture is stirred at room temperature, and 7.5 g. (0.06 moles) sodium carbonate monohydrate is added over a period of 20 min. The resulting mixture is stirred at room temperature for 1 hour. The mixture is extracted with 2 150 ml. portions of benzene. The benzene phases are combined, dried with anhydrous MgSO, and evaporated. There is obtained a yield of 20.0 g. (68.3 percent of theory) of the title compound, n 1.5460.

EXAMPLE 2 Preparation of 3-[O-0,0-diethylphosphorothioyl)]- benzaldoximino-N'-methy1 Carbamate Ten grams (0.034 moles) of 3-[O (O- diethylphosphorothioy1)] benzaldoxime dissolved in 10 m1. of acetone is treated with an excess of methylisocyanate. The mixture is poured into 200 ml. of benzene. The benzene is washed with 2- 50 ml. portions of water, dried with anhydrous MgSO.,, and evaporated. There is obtained a yield of l 1.2 g. (93.3

percent 'of theory) of the title compound, n 1.5394.

EXAMPLE 3 EXAMPLE 4 Preparation of 4-[O-(0,0-Diethylphosphorothioyl)] acetophenoneoximinoNmethyl Carbamate By an analogous procedure as given in Example 2, supra, 10.0 g. (0.03 moles) of 4-[O-(0,0- diethylphosphorothioyl)l-acetophenoneoxime is reacted with methyl isocyanate. There was obtained 1 1.5 g. (96.9 percent of theory) of the title compound.

EXAMPLE 5 Preparation of 4-[0,0-diethylphosphorothioyl]- acetophenoneoximino Acetate The following procedure also can be used with a carbamyl chloride, sulfonyl chloride or chlorofomate in order to obtain compounds that include the respective functional moieties typical of said reactants.

In ml. of benzene 10.0 g. (0.03 moles) of 4-[4- 0,0-diethylphosphorothioyl) ]-acetophenoneoxime, 3.2 g. (0.04 moles) of acetylchloride, and 4.1 g. (0.04 moles) of triethylamine are combined. The mixture is heated and refluxed for about 1 hour. The cooled reaction mixture is washed with two 50 ml. portions of water. The benzene phase is dried with anhydrous magnesium sulfate and then the benzene evaporated. There is obtained 11.0 g. (96.5 percent of theory) of the title compound n 1.5279.

EXAMPLE 6 Preparation of 4-[O-(0,0-diethylphosphorothioyl)] Benzaldoximino-N'morpholinylcarbamate Seven grams (0.07 moles of phosgene in 150 ml. of anhydrous diethyl ether is added to a 500 ml. threeneck flask fitted with a stirrer, dropping funnel, dry ice condenser, and thermometer. The solution is stirred and cooled to 10 C. with an ice bath. N,N- dimethylaniline, 8.6 g. (0.07 moles) is added over a period of 30 minutes. 4-[O-(0,0-

diethylphosphorothioyh] benzaldoxime, 14.5 g. (0.05 moles) in 50 ml. of anhydrous diethyl ether is added over a period of 30 minutes. The temperature of the reaction mixture is maintained between and C. After the addition is complete, the mixture is stirred for one hour at 15 C. A solution of 17.4 grams (0.2 moles) of morpholine and 10 ml. of water is added to the stirring reaction mixture at such a rate that the temperature does not exceed 15 C. After the addition is complete, the mixture is stirred for 2 hours at room temperature. The mixture is diluted with 200 ml. of ether and washed consecutively with 100 ml. of water, 100 ml. 1 N HCl, and again with 100 ml. of water. The ether phase is dried with anhydrous MgSO and evaporated to yield 18 grams (89.8 percent of theory) of 4-[O-(O,O-diethylphosphorotl'1ioyl)] benzaldoximino-N'-morpholinylcarbamate, n 1.5423.

EXAMPLE 7 The product is isolated by the procedure described in Example 6. There is obtained a 17.8 grams (94.8 percent of theory) of the title compound, n 1.5423.

EXAMPLE 8 Preparation of 4-[ O-( 0,0-diethylphosphorothioyl )1 Benzaldoximino-N [3 N ,N' '-diethylamino )ethyl] Carbamate.

Seven grams (0.07 moles) of phosgene, 8.6 grams (0.07 moles) of N,N-dimethylaniline, and 14.5 grams (0.05 moles) of 4-[O-(0,0-diethylphosphorothioyl)] benzaldoxime are reacted in 200 ml. of anhydrous diethyl ether by the procedure described in Example 6. The etherical solution is washed with 100 ml. of ice cold 1N HCl and returned to the reaction flask where it is stirred and cooled to 10 C. A solution of 1 1.6 grams (0.1 moles) of B -N,N-diethyl ethylenediamine and 10 ml. of water is added to the etherical solution at such a rate that the temperature does not exceed 15' C. After the addition is complete, the mixture is stirred at room temperature for 1 hour. An additional 100 ml. of anhydrous diethyl ether is added, and the mixture is washed with ml. of ice cold 1N NaOH followed by two 50 ml. portions of water. The ether phase is dried with anhydrous MgSO 4 and evaporated. There is ob tained 11.3 grams (51.8 percent of theory) of the title compound, n 1.5310.

The following is a table of the compounds prepared according to the aforedescribed procedures. Compound numbers have been assigned to each compound and are then used for identification throughout the balance of the application.

TABLE I Compound M. number R1 X Y C.) 1113 s 0 II 1. 5450 S o H 1.5520 s o C(O)NHC1 I3. 1. 5394 S O C(O)NHCH1 2 04-05 s o NI-ICH1CH=CH2 1. 5430 s o 1.5405 s o c o o1n 1. 5318 s o C(0)N CH 1.5354 .1 s o c o 1-111o1nc11=o11 1. 53:10 10.. s o momma-morn 1.5255 11 s o o 011 11 co13 1. 5458 [2. S 1. 5655 1:1. s o C(O)NH(,II3 1. 5538 1 1.. s o n 1. 5404 15.. s o C(O)NHCH:1 1.5400 111 s 0 C(O)NHCH(CH3)Q 1.5241 17. s o C(O)NHCH(CH1)- 1 1. 5421 l8 s o 11 1. 5110 11L 5 o C(O)NHCH3 1. 5436 20. s o C(O)NHCH1C 1. 5303 21 s o 11 1.5586 s o 1x00111011. 1.5510 S 0 H 1. 5348 S 0 C(O)NH-phenyl 1. 5670 s o C(O)NHCII(CH1)Z 1.53 S 0 01001115... 1. 5004 s o r 1. 5340 s o 1. 5592 s 0 1.5527 s o 1. 5303 S O P(S)(OC1H5)2 (Q s o ommrrcm 1 s o C(O)NHCH(CH;) 1 5263 s 0 C(O)NHCH:... 1 5195 S 0 C(O)NHCH(CH3 1 5128 s 0 CH; C(O)NHC l-I -u. 1 5163 S O owmucm 1 5005 S 0 o(o 1 111o11 0111)1 1 5378 S O c omuo1n 1 5486 S O C(O)C1I3 1 5543 S 0 C(O)CH3 15410 S 0 omucuL. 1 5413 S O C(O) NHCH2C1I: 1 5307 C umgound num er SSSSSSSSSSSSSSSSSSSSSSSOOOOSSS IIIIII 11111.11

w m H v1 n H w n a h m H v m "d M M X 0 u n n n n "m U m i u m mm u n 0 n mm} Im 1... w TL ITTII @3 H HHHHHaHHHHHHHHHHHQfiHHHunnnun 000000 0000000000000000000000000000000000000000000000000000000000000000000000 SSSSSS SSSSSSSSsSSSSSS SSSSSSSSSSSSSSSSSSSSSS SSS ssssssSSSSSSSSSSSS S mwmmm wow. 5 s vmm awwwwmmmwmwm s smmww s 5 00000 GCOCCCCCCCCCCCCCOCGCC000 0 wmw wwmmwww 0 000000 w mam mmn mn nmm m mmmmmm m 000 C c co c mmwmmmmw C CsHaO Compound M-P' number R R1 X Y Q (1 R2 R3 Q) S 0 CHa 4 CH3. C(O)N(C1H5)CH50H 1.5272 s 0 H 4 H-. C(O)NHC2H5OH 1.5423 S O H 4 1 5310 S O H 4 1.5647 s O H 4 1.5875 S O H 4 1.5750 S O H 4 5)2 1-5314 8 0 H 4 H C(O)NH-3-CH S-pheny1 1.5052 s 0 H 4 CH3... C(O)NH-3-CH S-phenyl 1.5049 s 0 H 4 CH1"... C(0)NH-2,4,5-triCl-phenyl- 109-111 s 0 H 4 CH3"... C(O)N(CHzOH=CI-I )z 1.5404 s o H 4 H C(O)NH-3-Ci-pl1enyl. L553) s 0 H 4 H o o NH3-cH3shen 1 1'5938 s o H 4 CH1 'C(O)CH2CH=CHg 1.5370 s o H 4 CH3, 01001. 145343 s 0 2-0 4 H C(O)NH-3-Cl-pl1enyl 1.5723 S O H 4 CH3 C(O)-l2-C4H9 1.5147 s o H 4 H ctomH-cnn 1.5252 s 0 H 4 H C(O)NH-3,4-di-Cl-phenyl 1.5720 s o H 4 H C(O)NH-4-Br-phenyl 11511:; S o H 4 CH1... C(O)NH(C11H17) 1.5216 s o H. 4 H C(O)Nl CH2C(O)OCzH5 1.5253 s 0 H... 4 H C(O)NH-4-CH S-phenyl. 1.5832 s o H. 4 H. (0 1711! 1.5550 s o H 4 H. C(O)N(CH1):.... 07-110 s 0 3-CH1 4 CH1 C(O)NH(i-C3H7) 1.5150 s 1 3-CH1 4 CH3 C(O)NH(CIIzCH 1.5293 s o 3-CH1... 4 c )N 1.5312 s 0 3-CH3- 4 1.5270 g 8 1 4 1.5000 4 1.5425

s 0 H 4 s 0 343111. 4 1.5574 s 0 3-CH3- 4 1.5186 s 0 3-CH1 4 1.5128 s 0 4 1.5564 s o H. 4 1.5777 s 0 H. 4 1.5105 s o 4 C(O)NH-4-Br-phenyl 1.5993 s o H. 4 C(O)NH-4-Br-phcnyl 0400 s 0 H. 4 C(O)NH(i-C1H7) 1.5274 s 0 H. 4 C(O)CHzS4-Cl-phenyl 1.0077 s 0 H 4 C(O)CHzS-4-Cl-pheny1. 1.5703 s o H. 4 1.5353 s 0 3-N 4 1.5455 s o H- 4 1.5752 s 0 33102 4 1.5833 s o 3-NO 4 1.54% s 0 H. 4 1.5403 s 0 H. 4 1.5632 s o H 4 1.5507

1 (p)=Position of phenyl substitution by 2 Decomposition.

3 Dark oil.

4 Semi-solid.

5 Wax-y solid.

HERBICIDAL SCREENING TESTS Novel compositions are phytotoxic compounds which are useful and valuable in controlling various plant species.

In the method ofth e present invention for controlling undesirable plants which comprises applying an herbicidally effective amount of the above-described compounds to the area in which control is desired, an herbicide is used to mean a compound which controls or modifies the growth of plants. By an herbicidally effective amount" is meant an amount of compound which causes a modifying efiect upon the growth of plants. Such modifying effects include all deviations from natural development, for example, killing, retar- 55 C=NOR3] relative to the phosphorus containing groups.

crispus (L.)), were planted in individual rows one-half inch deep in Santa Cruz sandy loam soil contained in compressed paper flats 8 V4 X 6 k inches, which are 2 inches deep. Enough seeds were planted to give about 30 to plants of each of the weed species in each flat. The flats were watered after planting. The following day each flat was sprayed at the rate of 20 pounds of the candidate compound under test in 80 gallons of solution per acre. An atomizer was used to spray the solution on the soil surface. The flats were placed in a greenhouse at 80 F. and watered regularly. Two weeks later the degree of weed control was determined by comparing the amount of germination and growth of each weed in the treated flats with weeds in several untreated control flats. The results of this test are reported in Table II.

Post-emergence Herbicide Test. The seeds of four weed species, crab grass (CG) (digitaria sanguinalis (L.) Scop.), watergrass (WG) (Echinochloa crusgalli (1..) Beauv.), red oats (RO) (Avena sativa (L.)), mustard (Md) (Brassica juncea (L.) Coss.), and one crop, pinto beans (PB) (Phaseolus vulgaris) were planted in individual rows as described in the pre-emergence test, supra. Two weeks after planting, the plant foliage was sprayed with a 0.5 percent solution of the test compounds at a rate equivalent to 12.5 pounds/acre. The treated plants were placed back in TABLE II Pre-Emergence Herbicide Test* Compound Number CG Ft WG PW M it -H 1551????:fififih i" i v i H H I- i i iiii i i iPiii.I.$i$i$IIiHHi-i. i ii v +H *Herbicidal Activity Rating: slight injury H- moderate injury +H- severe injury or death TABLE III Post-Emergence Herbicide Test* H -W iifiiiiifiii ii ii iii 1' HHH I' 1' P iii 1 42 *Herbicidal Activity Rating: um j y -H- moderate injury -H+= severe injury or death The compounds of the present invention are used as preemergence or post-emergence herbicides and are applied in a variety of ways at various concentrations. in practice, the compounds are formulated with an inert carrier, utilizing methods well known to those skilled in the art, thereby making them suitable for application as dusts, sprays, or drenches and the like in the form and manner required. The mixtures can be glispersed in water with the aid of a wetting agent or they can be employed in organic liquid compositions, oil and water, water in oil emulsions, with or without the addition of wetting, dispersing or emulsifying agents. The amount applied depends upon the nature of the seeds or plants to be controlled and the rate of 45 application varies from 1 to approximately pounds ;per acre.

' The phytotoxic compositions of this invention are applied to the plants in the conventional manner. Thus, the dust and liquid compositions can be applied to the 50 plant by the use of power-dusters, boom and hand sprayers and spray-clusters. The compositions can also be applied from airplanes as a dust or a spray because they are effective in very low dosages. In order to modify or control growth of germinating seeds or emerging seedlings, the dust and liquid compositions are applied to the soil according to conventional methods and are preferably distributed in the soil to a depth of at least one-half inch below the soil surface. It is not necessary that the phytotoxic compositions be admixed with the soil particles and these compositions can be applied merely by spraying or sprinkling the surface of the soil. The phytotoxic compositions of this invention can also be applied by addition to irrigation water supplied to 65 the field to be treated. This method of application permits the penetration of the compositions into the soil as the water is absorbed therein. Dust compositions,

granular compositions or liquid formulations applied i such on the surface of the soil can be distributed below the surface of the soil by conventional means such as discing, dragging or mixing operations.

The phytotoxic compositions of this invention can also contain other additaments, for example, fertilizers, pesticides and the like, used as adjuvant or in combination with any of the above-described adjuvants. Phytotoxicants useful in combination with the abovedescribed compounds include for example 2,4- dichlorophenoxyacetic acids, 2,4,5-trichlorophenoxyacetic acid, 2-methyl-4-chlorophenoxyacetic acid and the salts, esters and amides thereof; triazine derivatives,

as 2,4-bix( 3-methoxy-propylamino)-6- methylthio-S-triazine; 2-chloro-4-ethylarnino-6- isopropylamino-S-triazine, and isopropy1amino-6-methy1mercapto-S-triazine; urea derivatives, such as 3-(3,4dichloropheny1)-1 ,1- dimethyl urea and 3-(p-chloropheny1)-l,l-dimethyl urea, and acetamides such as N,N-dia11yl-a chloroacetamide, N-( a -chloroacetyl)hexamethy1ene imine, and N,N-diethylu -bromoacetamide, and the like; benzoic acids such as 3-arnino-2,5-dichlorobenzoic and; thiocarbamates, such as S-propyl dipropylthiocarbamate; S-ethyldipropylthiocarbamate, S-ethyl-cyclohexylethylthiocarbarnate, S-ethyl hexahydro-lH-azepine-l-carbothioate and the like. Ferti1- izers useful in combination with the active ingredients include, for example, ammonium nitrate, urea and superphosphate. Other useful additaments include materials in which plant organisms take root and grow such as compost, manure, humus, sand and the like.

The compositions of the present invention were tested as foliage fungicides. This test indicated protectant action against fungi attacking plant foliage. Pinto bean plants were sprayed with three concentrations of dissolved or suspended chemical in water, 1,000, 500 and 100 parts per million (ppm). The active compound was dissolved in an appropriate solvent and further dispersed in water, and for this purpose a surface active agent or wetting agent was employed to facilitate formulation of the dispersions. After the sprayed plants were dried, they were inoculated with powdery mildew spores (Erysiphe polygoni). Results were read when disease symptoms were distinct on untreated bean plants. Compound numbers 84 and 86 exhibited 75-99 percent control at 100 ppm. and compound number 85 exhibited 100 percent control at 100 ppm. of the powdery mildew infection with no phytotoxicity.

Insecticidal Evaluation Tests.

The following insect species were subjected to evaluation tests for insecticidal activity:

1. Housefly (HF) Musca domestica (Linn.)

2. German Roach (GR) Blattella germanica Linn.)

3. Salt-marsh caterpillar (SMC) Estigmene acrea 4. Milkweed Bug (MWB) Oncopeltus fasciatus (Dallas) 5. Lygus Bug (LB) Lygus hesperus (Knight) Aliquots of the toxicants, dissolved in an appropriate solvent, were diluted in water containing 0.002 percent of a wetting agent, Sponto 221 (a polyoxyether of a1- kylated phenols blended with organic sulfonates). Test concentrations ranged from 0.1 percent downward to that at which 50 percent mortality was obtained. In the 2-ethylamino-4- 14 tests, for these species, 10 l-month old nymphs of the German Cockroach and Lygus Bug and 2-week old nymphs of milkweed bug were placed in separate circular cardboard cages sealed on one end with cellophane and covered by a cloth netting on the other. Test concentrations for the Lygus Bug ranged from 0.05 percent downward to that at which 50 percent mortality was obtained. Each of the aqueous suspensions of the candidate compounds were sprayed onto the insects through the cloth netting by meansof a hand spray gun.

Percent mortality in each case recorded after 72 hours and the LD-SO values expressed as percent of toxicant in the aqueous spray was recorded.

For testing the Salt March Caterpillar, test solutions were prepared in an identical manner and at concentrations the same as for the German cockroach and the milkweed bug above. Sections of bitter dock (Rumex obtusifolus) leaves, 1 1.5 inches in length were immersed in the test solutions for 10 to 15 seconds and placed on a wire screen to dry. The dried leaf was placed on a moistened piece of filter paper in a Petri dish and infested with 5-3rd Instar larvae. Mortality of the larvae was recorded after 72 hours and the LD-50 values are expressed as percent active ingredient in the aqueous suspension.

The following procedure was used to test houseflies. A stock solution containing 100p.g/m1 of the toxicant in an appropriate solvent was prepared. Aliquots of this solution were combined with 1 milliliter of an acetonepeanut oil solution in a glass Petri dish and allowed to dry. The aliquots were there to achieve desired toxicant concentration ranging from 100p. g per dish to that at which 50 percent mortality was attained. The Petri dishes were placed in a circular cardboard cage, closed on the bottom with cellophane and covered on top with cloth netting. Twenty-five female houseflies were introduced into the cage and the percent mortality was recorded after 48 hours. The LD-50 values are expressed in tenns of u g per 25 female flies. The result of these insecticidal evaluation tests are given in Table IV.

TABLE IV (LD-50 Values) Compound Number HF GR LB SMC 38 3 7 0. 1 0.003 0. 1 39 8 0. 1 0.05 0.05 40 8 0. 1 0.03 0. 1 4 1 8 0. 1 0.05 0.08 42 50 0.] 0.05 0.05 46 8 0. 1 0.05 0.03 47 8 0. I 0.005 0.05 48 80' 01 0.05 0.l 49 5 0. 1 0.008 0. l 50 8 0. 1 0.05 0. l 5 1 50 0.l 0.05 O.l 52 10 0. 1 0.05 0. l 5 3 100 0.l 0.05 0.! 54 2.5 0.01 0.005 0.01 55 0.8 0.005 0.001 0.01 56 1.5 0.01 0.001 0.03 59 10 0. 1 0. 1 60 30 0. 1 0. 1 6 l 30 0. 1 0. 1 62 30 0. 1 0. 1 63 30 0. 1 0. 1 64 4 0.05 0.05 65 8 0.05 0.08 66 8 0. 1 0.03 0. l 67 15 0.] 0.03 01 68 40 0. 1 0.05 01 69 50 0.l 0.05 0.] 70 30 0.l 0.05 0.l 7 l 7 0. 1 0.03 0.05 78 8 0. 1 0.03 0.05

101 2.5 0.05 0.005 0.01 104 6 0.03 0.008 0.05 105 7 0.03 0.01 0.005 106 7 0.03 0.01 0.008 107 3 0.03 0.005 0.003 108 7 0.03 0.01 0.005 1 09 3 0.03 0.008 1 l 6 0.03 0.01 0.] 1 l l 7 0. l 0.03 0.03 l 12 7 0.] 0.05 0.1 l 18 4 0.1 0.008 121 8 0.1 0.01 0.03 122 0.1 0.01 0.1 124 5 0.05 0.005 0.01 126 5 0.1 0.008 0.] 130 5 0.03 0.003 0.01 133 5 0.l 0.05 0.] 137 6 0.1 0.005 0.03 138 5 0.1 0.03 0.01 142 6 0.03 0.003 0.05 143 4 0.03 0.01 0.03 149 5 0.03 0.03 0.03 152 4 0.08 0.008 0.05 155 4 0.l 0.03 0. l 157 3 0.05 0.008 0.01 165 6 0.03 0.01 0.001 171 3 0.03 0.005 0.03 172 3 0.01 0.005 0.005 185 8 0.l 0.01 0.l 186 9 01 0.03 0.1 187 5 01 0.01 0.l 191 4 01 0.005 0.05 192 2 0.03 0.003 0.03 195 7 01 0.05 0.l 200 8 0. l 0.03 0.05

In testing against milkweed bug representative LD-50 results obtained were for compound numbers 47, 55 and 56 0.01 percent; for compound numbers 49, 67 and 143 0.03 percent; compound numbers 64 0.05 percent; compound numbers 68 0.08 percent and compound number 54 0.008 percent.

Compound number 5 5 is extremely useful in the control of European corn borer (Pyrausta nubilalis (Hubner)).

The same test procedure as mentioned above for salt marsh caterpillar was used for cotton bollworm (Heliothis zea (Boddie)), except that leaves of Romaine lettuce were utilized as the host plant rather than bitter dock. The following compounds were found to be active against cotton bollworrn: the LD-SO values obtained were (5), (54) and (143) 0.005 percent; 0.01 percent; (13) 0.03 percent; (137) 0.001 percent; (55), (138), (141), and (142) 0.003 percent; and (56) 0.008 percent.

The compounds were also found to be active against two-spotted mite (Tetranychus urticae (Koch)). Lima beam plants (Phaseolus sp.) were utilized as the host plant and infested with 50 to mites of various ages. Twenty-four hours after infestation, they were sprayed to the point of run off with aqueous suspension of the toxicant. Test concentrations range from 0.05 percent to that at which 50 percent mortality was obtained. The following compounds exhibited LD-SO values of 0.005 percent (9) and (56); 0.001 percent (55) and 0.008 percent (46).

The compounds were also found to be active against Candidate test compounds, usually formulated in Tween-20 (polyoxyethylene (20) Sorbitan monolaurate), are administered orally by stomach tube at an initial dosage of 400 mgJKg. to fasted male Swiss albino mice. Two hours after treatment, the mice are killed by cervical dislocation and both thighs are dissected from each test animal and placed in labeled glass vials. Each vial is inoculated with 10 newly hatched black blow fly larvae (Phormia regina (Meigen)) and stored in an incubator at F. and 4050 percent relative humidity. Tissues from mice that die during the 2 hour holding period after administration of the compounds are processed in the same manner. After the larvae had fed on the tissues for 48 hours, the vials are examined and the percentage of larvae mortality in each is noted. If 80 percent or more of the larvae are killed at the initial dosage, successively lower dosages are then tested until the lowest dosage that killed at least 80 percent of the larvae is determined.

In this animal systemic insecticide evaluation test, compounds are tested further on guinea pigs, using the oral route of administration. The compounds are formulated as solutions or suspensions in Tween 20 and administered at an initial dosage of mgjKg. Twenty-four hours prior to treatment, the guinea pigs are wounded and the wounds infested with larvae of the black blow fly (Phormia regina (Meigen)). At 4 and 24 hours after treatment, stable flies (Stomoxys calcitrans (L. are fed on the guinea pigs. Engorged flies are held for 24 hours to see if they are killed by the blood they ingest. At 24 hours after treatment, the wounds are examined to see if the fly larvae are killed by the insecticide. If the larvae are alive, they are removed from the wounds. If any of the arthropods are killed at the initial dosage, the candidate insecticides are administered at lower dosages until there was no significant insecticidal activity. The following table gives the results of the mouse assay and guinea pig assay tests described above.

l7 18 TABLE V The following procedures describe the chemoprophylatic and chemotherapeutic efficacy tests Anlmal System19 Insectlclde Actlvlty utilized to demonstrate the animal parasitology activity of the phosphorus-containing oxime carbamate com- Lowest Dosage (mg/Kg) 5 positions of the present invention. Mouse Assay Guinea Pig Assay Test 1. Unparasitized weanling mice were offered *7 medicated food for l 2 days prior to inducing infecctivity Against trons, and for a total of 21 days infections were ad- Stable ministered per os using 100 300 embryonated 4 532$? 5 3: 2%; $82,, E51,? 10 ova/mouse of Syphacza obvelara (So) and 100 300 (mg/Kg) (mg/Kg) (mg/Kg) (mg/ g) embryonated ova/mouse of Aspzculuris letraptera (At).

A suitable number of unmedicated littennate mice 1 400 400 100 100 also received the above infection and served as control 2 to determine the comparative efiicacy of the medica- 3 400 100 100 50 25 4 200 [00 I00 25 12 trons. All mice were sacrificed after 21 days (the med1- 10 200 50 100 50 T00 cation period) and the residual parasites found in the g; 3% 2g 5 25 intestine were identified and counted. These counts in 33 400 30 gg 0 the medicated groups were compared to the un- 36 400 l9 400 200 100 100 50 2O medicated (controls) and a percent efficacy was as 39 I00 50 100 100 signed, (M/ICX100)'= percent eflicacy. 4 22 8 100 Test 2. weanling mice were housed together with 2 400 200 100 100 older pinworrn (So) and (At) infected mice in a box 0 400 200 100 100 100 with damp litter for 15 to 21 days to allow a heavy pin 2; if 8 6 g i 25 worm infection containing all stages of oxyurid (So and 66 200 so so 25 25 At) to naturally build up. At the end of this holding 67 period, the post-weanling littermates were weighed in- 84 200 100 200 100 50 86 400 200 100 100 100 dlvidually and dosed with the sub ect compounds 87 400 25 (suspended in Tween 20) on a body weight basis. One 94 200 100 100 100 50 133 100 200 to 3 days later, these truce were sacrificed and the 134 400 25 residual worms identified, counted and compared to 2 Z288 ig the unmedicated controls. Examples of efiicacy 0b- 137 100 50 served for six compounds of the present invention are 138 100 25 139 400 100 given in the following table. 141 50 144 400 100 145 400 100 TABLE VI {:2 Z288 Internal Animal Systemic Activity 149 50 25 150 400 200 Dosage: Efficacy 151 100 50 Compound Test (1) ppm or 152 200 200 Number Procedure (2) mg/kg So At 2 1 500 100 100 The test results indicate that these compounds are i i8 32 $2 biologically active and are useful as animal systemic in- 2 (2) 100 65 85 secticides. The compounds can be used as effective 9 (I) 500 100 100 f d 9 1 1000 100 100 parasiticides by applying them in a variety 0 ways an 17 (I) 1000 98 97 at various concentrations, depending upon the nature 7 1 00 0 55 and habitat of the parasite to be controlled. ig 3 g The candidate compounds were employed in an in I7 200 100 vitro tick assay. In this test unfed lone star tick nymphs 46 1 250 100 100 (Amblyomma americanum (L.)) were confined for 24 3 (2) 85 6 2 100 100 100 hours in cotton cloth that had been treated in acetone 66 (I) 1000 100 100 solutions of the test compounds. The percentage of 6 (2) 50 765 100 nymphal mortality was then observed. 1f percent or 55 $2 g 9 more of the nymphs were killed at the initial screening 76 2 100 100 98 level of 1.0 percent for a given compound, the com- 7 (l) 500 100 100 7 2) 50 95 95 pound was tested further at lower levels. The com- 19 (1) 2000 100 100 pounds 5, 11, 17,20, 23, 26, 31, 33, 36, 38, 61, 64 19 2) s0 70 and65 exhibited 80 percent or better control of the tick 60 g; E 33 2 nymphs at 0.5 percent. Compound number 29 ex- 48 (1) 250 100 100 hibited 80 percent or better control of the tick nymphs 48 50 85 at 0.1 percent and compound number 32 exhibited 80 g l 8 32 g percent or better control at 1.0 percent concentrations. 79 1 500 100 Compound number 28 at a concentration of 0.05 per- 65 79 (2) 55 92 0 t lethal to tick n m hs 86 (2) 50 9O 95 cent was better than 8 percen y p 87 (2) 50 100 100 Internal Ammal Parasite Systenuc systemic Tests. 88 (2 50 98 80 ml (2) 50 100 I I02 (2) 50 100 85 4 (l) 250 I00 100 l0 (1) 500 100 100 28 (l) 500 100 I00 70 (l) 250 95 87 134 (l) 500 100 100 135 (l) 500 I00 75 136 (l) 500 100 138 (l) 250 100 100 I39 (2) )0 100 100 I40 (1) 500 )0 l4] (1) 500 I00 144 (I) 500 I00 100 145 (l) 500 100 147 (l) 500 95 lOO 149 (l) 15 100 150 (2) 25 100 0 ll (2) I25 I00 100 152 (2) l2.5 100 100 The compounds of the present invention are useful as effective insecticides, herbicides, and external and internal animal parasiticides and are applicable in a variety of ways at various concentrations. In practice, the compounds are formulated with an inert adjuvant utilizing methods well known to those skilled in the art, thereby making them suitable for application and administration as dusts, sprays, drenches and the like in the form and manner required. The mixtures can be dispersed in water with the aid of a wetting agent or they can be employed in organic liquid compositions, oil-in-water, water-in-oil emulsions, with or without the addition of wetting, dispersing or emulsifying agents. Administration of said parasiticidal compositions to animal for systemic control of parasites can be in animal feedstufis which contain feed components of such as grain, grasses and the like, and certain beneficial additives such as vitamins, proteins, fats, minerals and carbohydrates. They can be given also in drinking water or skimmed milk, or in the form of tablets or capsules. Further methods of application include sprays, dyes, dips, dermal pour-on, subcutaneous administration, intramuscular injec-tion and the like. The exact dose to be administered to the animal is dependent upon the parasite to be controlled by the particular compound employed, as described herein, as well as upon whether the administration is to be a single dose or a multiple dose over a period of days. In general, it has been found that the systemic parasiticides of this invention can be administered orally or parenterally to warm blooded animals in amounts ranging from about 0.01 to about 600 milligrams per kilogram of body weight.

What is claimed is:

1. A compound having the formula in which X and -Y are independently selected from the group consisting of oxygen and sulfur;

R is selected from the group lower alkyl or lower alkoxy, having from one to six carbon atoms, inclusive;

R is selected from the group consisting of lower alkyl, and lower alkoxy having from one to six carbon atoms, inclusive;

Q is selected from the group consisting of hydrogen, and lower alkoxy having from one to four carbon atoms, inclusive;

R is selected from the group consisting of hydrogen, lower alkyl having from one to four carbon atoms and phenyl.

2. A compound according to claim 1 in which R is C H QR, isC l-LO, XisS,YisOandQisH,andthe C(R NOl-l group is in the nuclear 4-position in which R is H.

3. A compound according to claim 1 in which R is CH O, R is (ll-I 0, X is S, Y is O, Q is H, and the C(R 211011 group is in the nuclear 4-position in which R is 4. A compound according to claim 1 in which R is C H O,R isC H O,XisS,YisO,QisI-I,andthe C(Rg) NOl-I group is in the nuclear 4-position in which R is CH 

2. A compound according to claim 1 in which R is C2H5O, R1 is C2H5O, X is S, Y is O and Q is H, and the C(R2) NOH group is in the nuclear 4-position in which R2 is H.
 3. A compound according to claim 1 in which R is CH3O, R1 is CH3O, X is S, Y is O, Q is H, and the C(R2) NOH group is in the nuclear 4-position in which R2 is CH3.
 4. A compound according to claim 1 in which R is C2H5O, R1 is C2H5O, X is S, Y is O, Q is H, and the C(R2) NOH group is in the nuclear 4-position in which R2 is CH3. 